Down syndrome, one of the most common genetic causes of mental retardation associated with genetic factors, occurs in approximately 1.2 per 1000 live births, is typically caused by a nondisjunction of the 21st chromosome during meiosis resulting in a complete trisomy genotype, although atypical forms occur occasionally. Adults with Down syndrome have benefited from the advances in public health practices that have resulted in a dramatic extension in life expectancy. However, Down syndrome is still characterized by increased mortality rates during later stages of life. Causes of higher mortality rates later in life may be due to a number of factors, two of which are an increased risk for Alzheimer~s disease and an apparent tendency toward premature aging. Aging processes among adults with Down syndrome have been of interest for over 100 years because of the occurrence of the signs and symptoms of Alzheimer~s disease in the population. Indeed, brain tissue of virtually all adults with Down syndrome over 35 to 40 years of age displays significant accumulations of amyloid plaques, historically considered to be a hallmark of Alzheimer's disease neuropathology presumably due to the triplication and over expression of the gene for beta-amyloid precursor protein located on chromosome 21. The genotypic and phenotypic characteristics of the "oldest old" (i.e., 65 and older) adult population with mental retardation due to Down syndrome will be compared to those of their younger peers (also with Down syndrome) in order to identify genetic risk factors associated with survival and the cognitive declines associated with dementia of the Alzheimer~s-type. We have been able to identify a group of 100 people with Down syndrome 65 years of age or older. Investigation of this unique group of individualist will allow us to characterize the phenotype of the ~oldest old~ with Down syndrome and identify genetic and health status factors that are associated with extended survival and successful aging on one hand and the development of DAT on the other.